Molecular genetic studies in medulloblastomas: evidence for tumor suppressor genes at the chromosomal regions 1q31-32 and 17p13.

BACKGROUND

Medulloblastoma represents a common primitive neuroectodermal tumor of the cerebellum, the molecular pathogenesis of which has not been identified. Previous cytogenetic observations disclosed aberrations of chromosome 1 and 17 in medulloblastomas. In the present study, we have molecularly characterized the affected chromosomal segments.

PATIENTS AND METHODS

A panel of microsatellites on chromosomes 1 and 17 was used to assess allelic loss in 30 medulloblastomas and to characterize putative tumor suppressor loci.

RESULTS

36% of the medulloblastomas showed an interstitial loss of heterozygosity (LOH) on chromosome 1q. The common region of overlap was mapped between D1S1604 and D1S237 and included the locus F13B in the chromosomal region 1q31-q32.1. None of the MBs exhibited LOH of the telomeric portion of chromosome 1p which has been associated with several other human malignancies. 47% of the tumors showed LOH on chromosome 17p with a common region of overlap at 17p13.3. The lissencephaly gene 1 (LIS-1) was excluded as a candidate gene in this region.

CONCLUSION

Our data strongly suggest the involvement of putative tumor suppressor genes located on the chromosome arms 1q and 17p in the molecular pathogenesis of medulloblastoma.